TRIM52 is an E3 ubiquitin ligase with multifaceted cellular functions spanning innate immunity, proteostasis, and cell proliferation. As an antiviral protein, TRIM52 ubiquitinates Japanese encephalitis virus NS2A protein for proteasomal degradation, contributing to viral defense 1. Beyond viral immunity, TRIM52 serves as the key recognition component of the mammalian fMet/N-degron pathway, recognizing N-terminally formylated proteins through a conserved acidic loop and targeting them for degradation—a function critical for proteostasis and cell survival 1. TRIM52 also maintains genome integrity by limiting topoisomerase 2 adducts and preventing cell-cycle arrest, though it undergoes rapid proteasomal degradation by giant E3 ligases BIRC6, HUWE1, and UBR4/KCMF1 2. Clinically, TRIM52 is upregulated in multiple cancers including glioblastoma, lung cancer, and ovarian cancer, where it promotes proliferation and invasiveness through activation of Wnt/β-catenin and NF-κB signaling pathways 3, 4. In temporomandibular joint osteoarthritis, TRIM52 upregulation exacerbates inflammation and oxidative stress via TLR4/NF-κB pathway activation 5. These findings position TRIM52 as a promising therapeutic target for cancer and inflammatory diseases.